The recent discovery of microRNAs (miRNAs) and their ability to control global gene expression patterns may revolutionize current tissue engineering strategies. Altering cellular miRNA activity represents a unique mechanism for directing differentiation and tissue formation. Preliminary results obtained in our lab demonstrate that the transfection of hMSCs with specific miRNA mimics and inhibitors sensitizes these cells to osteoinductive signals, causing a more rapid presentation of bone-related markers in 2D cultures treated with osteogeneic media. The goal of this project is to evaluate the potential of miRNA-based strategies for improving current bone repair methods by testing the ability of miRNA-transfected hMSCs to regenerate bone in synthetic 3D scaffolds. This will be accomplished first by in vitro testing of the constructs in cell culture (Aim1) followed by in vivo studies of critical-sized bone mass defects in rats (Aim2). If successful, this project will demonstrate a novel utility for miRNA mimics and inhibitors and provide valuable support for the continued exploration of miRNA-based biomedical engineering techniques. PUBLIC HEALTH RELEVANCE: Stem cell-based therapies are quickly being developed to help tissue engineers regenerate bone mass for clinical applications. If successful, this project will identify a novel mechanism for enhancing bone formation in synthetic 3D tissue scaffolds and provide support for continued exploration of miRNA-based strategies for engineering tissues.